MICA

This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2014]

MHC Class I Polypeptide-Related Sequence A

Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T-cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis.

Cellular response to DNA damage stimulus Source: UniProtKB
Cytolysis Source: UniProtKB-KW
Defense response to bacterium Source: UniProtKB
Defense response to virus Source: UniProtKB
Gamma-delta T cell activation Source: UniProtKB
Immune response to tumor cell Source: UniProtKB
Natural killer cell mediated cytotoxicity Source: UniProtKB
Negative regulation of natural killer cell activation Source: CACAO
Negative regulation of natural killer cell mediated cytotoxicity Source: CACAO
Response to heat Source: UniProtKB
T cell mediated cytotoxicity Source: UniProtKB

Cytoplasm
Plasma membrane
Cell membrane
Note: Expressed on the cell surface in gastric epithelium, endothelial cells and fibroblasts and in the cytoplasm in keratinocytes and monocytes. Infection with human adenovirus 5 suppresses cell surface expression due to the adenoviral E3-19K protein which causes retention in the endoplasmic reticulum.

Anti-MICA antibodies and ligand shedding are involved in the progression of monoclonal gammopathy of undetermined significance (MGUS)to multiple myeloma.
Psoriasis 1 (PSORS1):
A common, chronic inflammatory disease of the skin with multifactorial etiology. It is characterized by red, scaly plaques usually found on the scalp, elbows and knees. These lesions are caused by abnormal keratinocyte proliferation and infiltration of inflammatory cells into the dermis and epidermis.
Psoriatic arthritis (PSORAS):
An inflammatory, seronegative arthritis associated with psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive, erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis).

Extracellular: 24-307
Helical: 308-328
Cytoplasmic: 329-383

N-glycosylated. Glycosylation is not essential for interaction with KLRK1/NKG2D but enhances complex formation.
Proteolytically cleaved and released from the cell surface of tumor cells which impairs KLRK1/NKG2D expression and T-cell activation.